Vimentin-positive, profibrogenic mesenchymal cells in intestine: Promising therapeutic targets for intestinal fibrosis

Vimentin is the major structural component of intermediate filaments in cells of mesenchymal origin such as fibroblasts, and myofibroblasts, which maintain the extracellular matrix (ECM) of the fibrous connective tissue. In wound healing process, these vimentin-positive mesenchymal cells play an important role by producing ECM molecules and its over-production finally leads to tissue fibrosis. A frequent complication of Crohn's disease (CD), one of the two major forms of inflammatory bowel disease, is fibrosis leading finally to intestinal strictures. The profibrogenic mesenchymal cells such as fibroblasts, myofibroblasts, and smooth muscle cell (SMC)-like cells are supposed to produce ECM proteins, accumulating prominently in the submucosa of intestinal fibrotic lesions of CD. There is a controversy about the origin of the fibrogenic cells in stricture lesions in CD. Mechanistic studies of intestinal fibrosis are difficult to perform in humans, therefore, we investigated the lesions of chronic fibrosing colitis induced by dextran sulfate sodium (DSS), with special relevance to the role of vimentin-positive mesenchymal cells in the lesions. Our investigations revealed that fibroblasts (vimentin(V)+)/α SMA(A)-) were increased in both mucosal and submucosal layer, while myofibroblasts (V+/A+) were increased in mucosal but not submucosal layers. Interestingly, irsogladine maleate, a drug for anti-ulcer disease, ameliorated inflammation and fibrosis in this chronic fibrosing DSS colitis with decreased number of these vimentin-positive mesenchymal cells. In conclusion, vimentin-positive profibrogenic mesenchymal cells cause intestinal fibrosis in the chronic DSS colitis model. Therefore, we suggest that these cells could be promising therapeutic targets in intestinal fibrosis of CD.